1. Field of the Invention
The present invention relates to a biological optical measurement instrument that measures biological information, specifically a signal indicative of a change in density in a light absorbing substance, by using light, and more particularly to a biological optical measurement instrument that makes cerebral activity visible by using data measured by optical biological measurement. The present invention relates also to a biological optical measurement instrument that makes visible other physiological changes, not only cerebral activity.
2. Description of the Related Art
The use of light having the peak intensity at a wavelength in a range from the visible region and the near-infrared region, and having high transmittance in vivo, makes it possible to noninvasively measure biological information. This measurement is based on Lambert-Beer's law explaining that the logarithm of a light signal measured is proportional to the product of an optical path length and a density. An extension of this law has led to development of technology for measuring a signal indicative of a relative change in concentration of hemoglobin (Hb) in vivo (hereinafter called an “Hb signal”). The Hb signals measured are of two types on “oxyhemoglobin (oxy-Hb)” and “deoxyhemoglobin (deoxy-Hb),” which will be called an “oxy-Hb signal” and a “deoxy-Hb signal,” respectively. There has been a proposal of technology using the above technology for multiple measurements of the Hb signals in the human cerebral cortex and for cerebral function imaging (see Medical Physics 22, pp. 1997-2005, 1995), which is spreading out into researches and clinical practices in the field of cranial nerve science. Because of being unable to form an accurate estimate of an effective optical path length, this technology measures the Hb signals based on the relative changes, and calculates the Hb signals, using data measured during a “time period of absence of cerebral activity to be measured” (i.e., inactivity data) as the reference. In addition, to measure a physiological change other than cerebral activity, the technology calculates the Hb signals, using data measured during a “time period of absence of physiological change to be measured” as the reference. Fundamental equations for calculations will be given below.
Letting λ be a wavelength and t be time, the intensity T(l, t) of transmitted light (or the inactivity data) measured during the “time period of absence of cerebral activity to be measured” can be expressed by Equation (1):−ln[T(l,t)]=eoxy(l)Coxy(t)d+edeoxy(l)(Cdeoxy(t)d+a(l,t)+sc(l)  (1)where eoxy(l) and edeoxy(l) represent molecular extinction coefficients of the oxy-Hb and the deoxy-Hb, respectively, at the wavelength λ; Coxy(t) and Cdeoxy(t), oxy-Hb concentration and deoxy-Hb concentration, respectively, at the time t; d, an effective optical path length; a(l, t), absorption of anything other than the hemoglobin (Hb); and sc(l), attenuation caused by scattering in vivo. On the other hand, the intensity TS(l, t) of transmitted light in the occurrence of the cerebral activity can be expressed by Equation (2):−ln[TS(l,t)]=eoxy(l)CSoxy(t)d+edeoxy(l)CSdeoxy(t)d+aS(l,t)+scS(l)  (2)where the superscript “S” indicates a value measured during the cerebral activity. Assuming that a light absorbing substance that undergoes changes during the cerebral activity is the hemoglobin (Hb) alone and that the absorption of anything other than the hemoglobin (Hb) and the scattering are fixed (a(l,t)=aS(l,t), sc(l)=scS(l)), subtracting Equation (2) from Equation (1) leads to Equation (3) holding:
                              -                      ln            ⁡                          [                                                                    T                    S                                    ⁡                                      (                                          l                      ,                      t                                        )                                                  /                                  T                  ⁡                                      (                                          l                      ,                      t                                        )                                                              ]                                      =                                                                                                  e                    oxy                                    ⁡                                      (                    l                    )                                                  ⁡                                  [                                                                                    C                        oxy                        S                                            ⁡                                              (                        t                        )                                                              -                                                                  C                        oxy                                            ⁡                                              (                        t                        )                                                                              ]                                            ⁢              d                        +                                                                                e                    deoxy                                    ⁡                                      (                    l                    )                                                  ⁡                                  [                                                                                    C                        deoxy                        S                                            ⁡                                              (                        t                        )                                                              -                                                                  C                        deoxy                                            ⁡                                              (                        t                        )                                                                              ]                                            ⁢              d                                =                                                                      e                  oxy                                ⁡                                  (                  l                  )                                            ⁢              D              ⁢                                                          ⁢                                                C                  oxy                                ⁡                                  (                  t                  )                                                      +                                                            e                  deoxy                                ⁡                                  (                  l                  )                                            ⁢              D              ⁢                                                          ⁢                                                C                  deoxy                                ⁡                                  (                  t                  )                                                                                        (        3        )            where DCoxy(t)=[CSoxy(t)−Coxy(t)]d and DCdeoxy(t)=[CSdeoxy(t)−Cdeoxy(t)]d, which are defined as the oxy-Hb signal and the deoxy-Hb signal, respectively. Since it is difficult to determine the effective optical path length d, these relative value signals (i.e., the oxy-Hb signal and the deoxy-Hb signal) are used to evaluate the cerebral activity. Since the light in the region visible to near-infrared for use in measurement has varying optical absorption properties depending on the oxygenated state of the hemoglobin (Hb), dual-wavelength spectrophotometry is used to derive Equation (3) for two wavelengths. This is taken as simultaneous equations, which in turn are solved to determine the oxy-Hb signal and the deoxy-Hb signal (i.e., DCoxy(t) and DCdeoxy(t)).
Although at the time of start of measurement (or at the period of pre-stimulation) an initial value can be simply calculated to determine the inactivity data, correction is required in order to enable detection of desired cerebral activity, because the resultant signal can possibly contain a change over a long period of time regardless of the cerebral activity.
The basic principle of this technology is to evaluate the status of cerebral activity, assuming that a local increase in the quantity of blood involved in activity of human sensory or motor function is defined as changes in the oxy-Hb signal and the deoxy-Hb signal. Typical changes involved in the cerebral activity are known as an increase in the oxy-Hb signal and a decrease in the deoxy-Hb signal. This results from an increase in the flow of blood for the purpose of compensating for oxygen and glucose consumed by metabolic activity caused by nerve activity. The increased blood is arterial blood containing oxygen, and an increase in an excessive amount of arterial blood, as compared to the amount of oxygen consumed, can possibly result in the increase in the oxy-Hb signal and the decrease in the deoxy-Hb signal. It is also generally known that such a change in the quantity of blood lags about 5 to 7 seconds behind the nerve activity. Thus, conventional researches set varying stimulations or thematic tests according to cerebral function to be measured, but nevertheless they adopt basically the same measurement paradigm and analysis method for all cerebral function to be measured from the viewpoint of time. Specifically, a general method involves setting a time interval between stimulations to about 20 to 40 seconds, and repeating the stimulation a plural number of times, thereby obtaining a cerebral activity signal, assuming that the Hb signals start changing in 5 to 7 seconds after the start of the stimulation and likewise start returning to their base lines in 5 to 7 seconds after the completion of the stimulation. This is supported by such hypothesis that “the change in the quantity of blood involved in the nerve activity occurs after a time lag of about 5 to 7 seconds behind the nerve activity.” Also adopted as the analysis method is the approach of using linear data, e.g., the linear data formed by linking the average of values measured for a duration of 5 seconds before the start of the stimulation to the average of values measured for a duration of 5 seconds between the instant after a lapse of 10 seconds, and the instant after a lapse of 15 seconds, after the completion of the stimulation. Here, as “inactive condition data” for calculation, an assumption that “inactive period during which cerebral activity is assumed to be absent” is defined as a period of a few seconds before the start of the stimulation and a period after a lapse of 5 to 7 seconds after the completion of the stimulation (or equivalently, provided that inactive time parameters are set). Also when the value measured before the start of the stimulation (e.g., the average of the values measured for a duration of 5 seconds before the start of the stimulation) is used as the reference to calculate the Hb signals, base line correction using linear fitting or frequency filtering takes place. Here, the “time period of absence of cerebral activity to be measured” is defined as the period before the start of the stimulation and the period after a lapse of 5 to 7 seconds after the completion of the stimulation (e.g., provided that the average of the values measured for a duration of 5 seconds before the start of the stimulation and the average of the values measured for a duration of 5 seconds between the instant after a lapse of 10 seconds, and the instant after a lapse of 15 seconds, after the completion of the stimulation are used as the reference).
Statistical evaluation of the presence or absence of the cerebral activity, and if any, the intensity thereof requires a representative value indicative of the activity. However, also in this case, calculation has been heretofore done to determine the representative value (e.g., the average or peak of values measured for the duration between the instant after a lapse of 10 seconds, after the start of the stimulation, and the instant of completion of the stimulation). Here, it is assumed that the change with time (or the “time period of absence of cerebral activity to be measured”) be defined in the same manner as above mentioned, regardless of the cerebral function to be measured (or equivalently, provided that active time parameters are set).
It has been shown that this technology enables measurement of cerebral function such as vision, motion, speech or short term memory, and the technology is widely used for clinical practices and cognitive science researches.
As for the sense of taste, cerebral function measurement using functional Magnetic Resonance Imaging (fMRI) has hitherto been the mainstream. This method involves making measurements on a subject in an unusual situation such as a case where the subject is given a sample of taste in extremely low doses through a tube put in his or her mouth with the subject fixedly placed on his or her back amid very loud noises. Besides this method, a gustatory perception evaluation apparatus using an electroencephalograph is disclosed in Japanese Patent Publication No. Hei 3-74572. There is also provided a description of a discussion on cerebral function measurement for the sense of taste, using optical biological measurement, as given in NeuroImage 31, pp. 796-806, 2006.